Pilomatricoma in the infraorbital region

Key Clinical Message Pilomatricoma, a rare benign skin tumor arising from hair follicle matrix cells, warrants consideration in the evaluation of subcutaneous nodules or masses, especially when presenting as painless and firm lesions. Accurate diagnosis hinges on histopathological examination, underscoring the significance of clinician vigilance and prompt intervention. Abstract Pilomatricoma, also referred to as Pilomatrixomas or Calcifying epithelioma of Malherbe, is a rare benign skin tumor derived from hair follicle matrix cells, presents a diagnostic challenge due to its diverse clinical manifestations. Females are more commonly affected by Pilomatricoma. This condition typically manifests as a painless, firm, and slowly progressive lesion. Histopathological analysis shows characteristic findings, such as basaloid cells at the periphery and shadow cells centrally. Immunohistochemical studies assess the expression of cytokeratin's associated with hair matrix differentiation. Complete surgical excision remains the cornerstone of treatment, ensuring favorable outcomes and minimizing the risk of recurrence. Awareness of this entity among clinicians is essential for timely recognition and appropriate intervention. In this specific case‐study, we present a case of Pilomatricoma situated in the lower left orbital region of a 32‐year‐old male individual who had been noticing swelling in that vicinity over the preceding 7 months.

sents a diagnostic challenge due to its diverse clinical manifestations.Females are more commonly affected by Pilomatricoma.This condition typically manifests as a painless, firm, and slowly progressive lesion.Histopathological analysis shows characteristic findings, such as basaloid cells at the periphery and shadow cells centrally.Immunohistochemical studies assess the expression of cytokeratin's associated with hair matrix differentiation.Complete surgical excision remains the cornerstone of treatment, ensuring favorable outcomes and minimizing the risk of recurrence.Awareness of this entity among clinicians is essential for timely recognition and appropriate intervention.In this specific case-study, we present a case of Pilomatricoma situated in the lower left orbital region of a 32-year-old male individual who had been noticing swelling in that vicinity over the preceding 7 months.

K E Y W O R D S
basaloid cells, cytokeratin, hair follicles, infraorbital region, Pilomatricoma, shadow cells/ ghost cells, skin tumor and lower extremities. 2,6It presents as asymptomatic, firm, solitary, slow-growing, painless nodule along with superficial ulceration, or bluish discoloration. 1 Typically, Pilomatricoma present as singular lesions, although multiple lesions can occur in association with conditions such as Steinert myotonic dystrophy, familial adenomatosis, Rubinstein-Taybi syndrome, Gardner's syndrome, Turner syndrome, and sarcoidosis. 6,7The report provides a comprehensive overview of a case concerning a 32-year-old male patient who was diagnosed with a Pilomatricoma situated in the left infraorbital region.

| CASE HISTORY/ EXAMINATION
A 32-year-old male visited the Department of Oral Medicine and Radiology, reporting swelling in the left infraorbital region persisting for 7 months.Upon examination, a small, soft, mobile mass measuring approximately 1 cm × 1 cm was observed in the left infraorbital rim area.The mass was non-tender upon palpation (Figure 1).

| METHODS
The differential diagnosis was dermoid and sebaceous cyst.Following the examination, surgical excision was performed under general anesthesia.The biopsy tissue extracted during the procedure was preserved in a 10% formalin solution and forwarded for additional histopathological analysis.Macroscopic examination revealed a single piece of tissue, exhibiting a grayish-white to light brown hue.It displayed a firm consistency and measured approximately 0.9 cm × 0.8 cm (Figure 2).Histopathological examination by routine hematoxylin and eosin (H and E) staining shows a well circumscribed, lobulated dermal adnexal neoplasm.Upon lower magnification examination, clusters of basaloid cells with round to oval hyperchromatic nuclei and increased mitotic activity were observed (Figures 3   and 4).These cells also exhibit abrupt keratinization along with structureless eosinophilic cells lacking nuclei called as ghost cells or shadow cells (Figure 5).The surrounding stroma shows foreign body giant cell reaction, chronic inflammatory cells and moderate vascularity.After correlating the clinical presentation with the histopathological findings, the diagnosis of Pilomatricoma located in the infraorbital region was confirmed.
Pilomatricoma is a benign neoplasm derived from hair matrix cells associated with βcatenin gene CTNNB1 mutation. 3,8βcatenin serves as a downstream mediator in the Wnt signaling pathway, regulating various cellular processes including cell differentiation within the hair follicle, cell adhesion, and cell proliferation.Mutations occurring in exon 3 of the CTNNB1 gene induce an upsurge in βcatenin levels, consequently contributing to the formation of neoplasms characterized by hair matrix differentiation.Approximately, 26%-100% of pilomatrixomas are associated with βcatenin gene mutations. 4 outlines the four identifiable morphological phases of Pilomatricoma: early, fully developed, early regressive, and late regressive. 6t has bimodal age distribution, predominantly seen in the first and second decades of life and another peak in the 55-65-year age group of patients. 4,7During examination, the Pilomatricoma exhibits distinctive signs such as the "tent sign" when the skin is stretched over the tumor, and the "teeter-totter sign" where pressure on one side of the lesion causes protrusion on the opposite side, resembling a seesaw motion.These signs are pathognomonic, providing crucial diagnostic indicators for pilomatricoma. 6The clinical presentation of Pilomatricoma may be confused with several other conditions, leading to a broad range of differential diagnoses.These include epidermoid cysts, dermoid cysts, chalazion, capillary hemangiomas, sebaceous adenoma, juvenile Xanthogranuloma, and rhabdomyosarcoma (Table 1). 8,9he final diagnosis of Pilomatricoma is based on the histopathological findings.Fine needle aspiration cytology (FNAC) can also be used as a preoperative diagnostic tool. 10,11The radiological techniques are least helpful but ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) can aid in preoperative diagnosis. 7Histopathological examination shows peripheral islands of basaloid cells and central areas of shadow cells. 8The basaloid cells are basophilic round cells with centrally located prominent vesicular nucleus and few cytoplasm. 12As the tumor matures, its constituent cells undergo changes.They acquire more cytoplasm, lose their nuclei, and transform into eosinophilic cells known as "shadow" or "ghost" cells.Additionally, in long-standing cases of Pilomatricoma, areas of calcification and ossification may also become visible within the tumor. 6n 1931, Rywkind and Shiltzow initially termed ghost cells as "Rote Zellen," a name originally applied to the undifferentiated cord of craniopharyngiomas.Later, Rywkind proposed a new name, "Verhornte epithelzellen," which translates to keratinized epithelial cells, indicating the nature and origin of the ghost cells. 13It was first described in Pilomatricoma by Highman and Ogden as dyskeratotic cells in 1936. 13,14In 1937, Robinson introduced the term "ghost cells" to describe the degenerative changes observed in the stellate reticulum cells during the formation of microcysts.Ghost cells are pale, eosinophilic having swollen cytoplasm and absence of nucleus.The term ghost cell was derived due to its hazy or shadowy, indistinct and structure less appearance in the H and E-stained sections.4][15] The various theories [14][15][16][17] regarding the formation of ghost cells have been summarized in a Table 2. Ghost cells can be found in several conditions such as calcifying odontogenic cysts, Pilomatricoma, dentinogenic ghost cell tumors, ghost cell odontogenic carcinomas, odontomas, ameloblastomas, ameloblastic fibromas, and craniopharyngiomas. 14,15istopathological analysis for Pilomatricoma often involves distinguishing it from several other skin conditions.These include basal cell carcinoma, tricholemmal cysts, trichoblastoma, and pilomatrix carcinoma (Table 3). 9imzu et al. conducted immunohistochemical studies and observed the expression of HKN-2, HKN-4, and HKN-7 cytokeratin's within the epithelial aggregates.These findings mirror the cytokeratin expression pattern typically found in the inner layers of the cortex of the hair shaft, thereby confirming the metrical differentiation characteristic of Pilomatricoma. 12Reigner et al. and Cribier et al. identified the expression of keratin hHb1, which is typically found in intermediate cells. 18,19This discovery provides additional evidence supporting the differentiation of cells within this neoplasm into cells resembling those of the hair cortex.The presence of Osteopontin and BMP-2 expression in shadow cells or ghost cells provides further evidence supporting their role in the formation of areas of calcification and ossification within Pilomatricoma.Trichohyalin, along with its related proteins like Filaggrin and Involucrin, are detected in intermediate cells.It is believed that these proteins play a role in the transformation F I G U R E 6 Morphological stages of pilomatricoma.

Condition Histopathological features
Epidermoid cyst Keratin-filled cyst lined by stratified squamous epithelium.

Dermoid cyst
Cyst containing skin adnexal structures like hair follicles and sebaceous glands.

Chalazion
Inflammatory reaction to the eyelid, often with pain & swelling; granulomatous tissue and lipid-filled macrophages.

Capillary hemangioma
Red or bluish-red vascular lesions; Proliferation of capillary blood vessels.

Sebaceous adenoma
Raised, smooth, yellowish nodules on the skin; Adenomatous proliferation of sebaceous gland cells.

Juvenile Xanthogranuloma
Yellow-orange papules or nodules, commonly in children; Proliferation of histiocytes with foamy cytoplasm and touton giant cells.

Rhabdomyosarcoma
Soft tissue mass with rapid growth, pain, or bleeding; malignant tumor showing evidence of skeletal muscle differentiation.
of these cells into keratinized shadow or ghost cells within pilomatricoma. 12able 4 summarizes the different treatment options for pilomatricoma. 3,6The primary treatment for Pilomatricoma involves wide surgical excision with 1-2 cm of clear margins to alleviate the risk of malignant transformation and recurrence at the site. 1 Additional treatment modalities mentioned in Table 4 include punch incision and curettage. 16Erol et al. reported a similar case involving a 44-year-old female with a painless, mobile mass palpable under her right eye, which was managed with complete surgical excision.The patient underwent a 24-month follow-up period without experiencing any signs or symptoms of recurrence. 1 In cases of giant Pilomatricoma, the surgical excision often results in a large defect that requires reconstruction.Local flaps are advantageous for this purpose due to their excellent color matching.Nadershah et al. reported a case involving a 28-year-old male with a Pilomatricoma presenting as a left facial mass.Following complete surgical excision, the resulting large cheek defect was successfully reconstructed using a cervicofacial flap.
The recurrence rate is very low and the incidence of recurrence is around 0%-3%. 1,2,11The malignant transformation of Pilomatricoma is very rare but malignant transformation can be suspected in cases showing recurrences. 1,6The literature reports three documented cases of pilomatrix carcinoma arising in areas previously excised for pilomatricoma. 4ilomatricoma presents a diagnostic challenge due to its rarity and varied clinical presentations.It is essential for clinicians to be well-informed about this lesion.Careful screening and thorough clinical examination are crucial for identifying suspected cases, which should then be confirmed through histopathological examination for an accurate diagnosis.Early detection and treatment are essential for achieving better cosmetic outcomes and minimizing the risk of malignant transformation.Wide surgical excision is the preferred treatment to minimize the chances of local recurrence and prevent malignant transformation from the existing lesion.

| PATIENT PERSPECTIVE
The patient will likely appreciate the treatment's effectiveness in removing the lesion and preventing recurrence or malignant transformation.They will also value the aesthetic outcomes of the reconstruction, particularly the use of local flaps for better color matching and minimal scarring.

| CONCLUSION
Pilomatricoma presents a diagnostic challenge due to its rarity and variable clinical presentation.It is crucial for clinicians to be well-informed about this lesion and maintain a high level of suspicion, especially when encountering subcutaneous nodules or masses in patients.Careful screening and thorough clinical examination are essential steps in identifying suspected cases, followed by confirmatory histopathological examination for accurate diagnosis.
Early detection is key to prompt and effective treatment.Complete surgical excision with clear margins is the mainstay of treatment for Pilomatricoma.Adequate surgical removal not only ensures accurate diagnosis but also leads to favorable outcomes and reduces the risk of recurrence.

Intralesional injections
Injection of medications directly into the tumor to shrink it.
T A B L E 4 Treatment modalities.

Figure 6 F
I G U R E 1 Clinical presentation.F I G U R E 2 Macroscopic findings.

F I G U R E 3
Scanner view showing islands of basaloid cells (black arrow) and ghost cells (white arrow).F I G U R E 4 Islands of basaloid cells (black arrow) and ghost cells (white arrow) in 10x magnification.F I G U R E 5 Ghost cells in 40x magnification (black arrow).